In a female patient with systemic lupus erythematosus who received high‑dose prednisolone for a flare and continued it for six weeks without tapering, what is the most likely cause of death?

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Perforated Duodenal Ulcer (Answer: A)

The most likely cause of death in this patient is a perforated duodenal ulcer, resulting from prolonged high-dose prednisolone use without appropriate tapering or gastroprotection. 1, 2

Why Perforated Duodenal Ulcer is the Answer

Direct Corticosteroid Gastrointestinal Toxicity

  • Prolonged high-dose corticosteroid use significantly increases the risk of gastrointestinal bleeding and perforation, with this patient's dose and duration (6 weeks of continuous prednisolone without tapering) far exceeding standard safety protocols 1

  • The FDA label for prednisolone explicitly warns that "steroids should be used with caution in active or latent peptic ulcer" and notes that "signs of peritoneal irritation following gastrointestinal perforation in patients receiving corticosteroids may be minimal or absent" 2

  • Patients on prolonged high-dose corticosteroids require proton pump inhibitor prophylaxis to prevent ulcer formation and perforation, which was clearly not provided in this case 1

Clinical Presentation Consistent with Perforation

  • Sudden death at home suggests rapid cardiovascular collapse from peritonitis and septic shock, which is the typical presentation of perforated peptic ulcer 1

  • Perforated ulcers can present with minimal warning in patients on corticosteroids because steroids mask inflammatory symptoms and blunt the febrile response, making the diagnosis particularly insidious 1

Violation of Fundamental Management Principles

  • This patient continued prednisolone for 6 weeks without tapering, which violates fundamental corticosteroid management principles 1

  • Guidelines specifically state that patients taking more than 20 mg of prednisolone for >6 weeks have an increased risk of short-term surgical complications, including a five-fold risk of infectious complications 3

Why Not the Other Options

Hypertensive Brain Hemorrhage (Option C)

  • While hypertension is a recognized comorbidity in SLE patients and corticosteroids can exacerbate blood pressure 3, 4, the clinical scenario of sudden death at home in a patient on prolonged high-dose steroids without gastroprotection points more directly to gastrointestinal perforation

  • The FDA label emphasizes gastrointestinal perforation as a specific risk with corticosteroids, with the warning that signs may be "minimal or absent" 2

Infection as Alternative Consideration

  • Infection is indeed a major cause of mortality in patients on corticosteroids, accounting for 24% of all deaths in severe conditions requiring corticosteroids 1

  • Research shows that early deaths (within first two weeks) are mainly due to disease activity while later deaths are mainly due to infection 5

  • However, at 6 weeks, perforated duodenal ulcer represents the most direct consequence of prolonged high-dose steroid use without appropriate gastroprotection 1, 2

Critical Clinical Pitfalls

  • Never continue high-dose corticosteroids beyond 6 weeks without a clear tapering plan 1

  • Always prescribe proton pump inhibitor prophylaxis when initiating high-dose corticosteroids, especially for courses exceeding 3-4 weeks 1

  • Monitor for gastrointestinal symptoms, though recognize that corticosteroids mask inflammatory signs and patients may present with minimal warning 1, 2

  • The concomitant use of NSAIDs with corticosteroids further increases gastrointestinal risk and should be avoided 2

References

Guideline

Perforated Duodenal Ulcer as a Cause of Death in Patients on Prolonged High-Dose Corticosteroid Therapy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Corticosteroids in Lupus.

Rheumatic diseases clinics of North America, 2016

Research

Methylprednisolone in systemic lupus erythematosus.

Singapore medical journal, 1990

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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